A facile and sensitive method of quantifying glutaminase binding to its ninhibitor CB-839 in tissues  

作　　者：Yicheng Chen Yiqing Zhao David L.Bajor Zhenghe Wang J.Eva Selfridge 

机构地区：[1]Department of Genetics and Genome Sciences,Case Western Reserve University,10900 Euclid Avenue,Cleveland,OH,44106,USA [2]Department of Medicine,Case Western Reserve University,10900 Euclid Avenue,Cleveland,OH.44106,USA [3]Case Comprehensive Cancer Center,Case Western Reserve University,10900 Euclid Avenue,Cleveland,OH,44106,USA [4]Seidman Cancer Center,University Hospitals Cleveland Medical Center,WOO Euclid Avenue,Cleveland,OH,44106,USA

出　　处：《Journal of Genetics and Genomics》2020年第7期389-395,共7页遗传学报（英文版）

基　　金：the Case Comprehensive Cancer Center's K12 award(5K12CA076917-22);the Clinical and Translational Science Collaborative TL1 training grant(1TL1TRO02549-01);NIH grants RO1CA196643,UH2CA223670,P5OCA150964,and P30 CA043703;a Stand Up to Cancer Colorectal Cancer Dream Team Translational Research Grant(SU2C-AACR-DT22-17).Stand Up to Cancer is a program of the Entertainment Industry Foundation.

摘　　要：Many cancer types reprogram their metabolism to become addicted to glutamine.One of the critical enzymes in the utilization of glutamine in these cells is glutaminase.CB-839(telaglenastat)is a drug that targets glutaminase that is currently being evaluated in many clinical trials for efficacy in various cancer types that are known to be driven by glutamine metabolism.Despite its use,there are limited assays available for testing the pharmacodynamic on-target effects of CB-839 on the limited,small-volume patient samples that are obtained in early-phase clinical trials.Thus,we developed an assay based on the cellular thermal shift assay technique using AlphalLlSA technology to show that CB-839 specifically engages glutaminase in colon cancer cell lines in vitro and in minute quantities of mouse xenograft tumors.Notably,we show that this assay detects CB-839 binding to glutaminase in platelets of patients collected while receiving CB-839 on a clinical trial.This assay may be used to study the pharmacodynamic profile of CB-839 in very small tissue samples obtained from patients on a clinical trial and may be useful infuture studies designed to screen other in hibitors of glutaminase.

关 键 词：GLUTAMINASE Method CANCER 

分 类 号：R914[医药卫生—药物化学]